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Information on EC 2.6.1.62 - adenosylmethionine-8-amino-7-oxononanoate transaminase and Organism(s) Mycobacterium tuberculosis and UniProt Accession P9WQ81
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EC Tree
2.6.1.62 adenosylmethionine-8-amino-7-oxononanoate transaminaseIUBMB Comments
A pyridoxal 5'-phosphate enzyme. S-adenosylhomocysteine can also act as donor.
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Word Map
- 2.6.1.62
- biotin
- tuberculosis
-
dapas
- analysis
-
quinonoid
- dethiobiotin
-
antepenultimate
- pyridoxal
-
auxotrophic
-
transamination
-
5'-phosphate-dependent
-
half-reaction
-
bicistronic
- s-adenosylmethionine
-
plp-dependent
-
biotinylated
- pimeloyl-coa
-
alpha-amino
- biotechnology
- pharmacology
The taxonomic range for the selected organisms is: Mycobacterium tuberculosis
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Synonyms
7,8-diaminopelargonic acid synthase, bio3-bio1, dapa aminotransferase, 7,8-diaminopelargonic acid transaminase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
7,8-diaminononanoate transaminase
-
-
-
-
7,8-diaminopelargonic acid aminotransferase
7-keto-8-aminopelargonic acid aminotransferase
-
-
-
-
7-keto-8-aminopelargonic acid-7,8-diaminopelargonic acid aminotransferase
-
-
-
-
DAPA aminotransferase
-
-
-
-
DAPA synthase
-
-
-
-
DAPA transaminase
-
-
-
-
diaminopelargonate synthase
-
-
-
-
S-adenosyl-L-methionine:8-amino-7-oxononanoate aminotransferase
-
-
synthase, diaminopelargonate
-
-
-
-
7,8-diaminopelargonic acid aminotransferase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + 8-amino-7-oxononanoate = S-adenosyl-4-(methylsulfanyl)-2-oxobutanoate + 7,8-diaminononanoate
enzyme shows a Ping Pong Bi Bi kinetic mechanism with strong substrate inhibition
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
amino group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:8-amino-7-oxononanoate aminotransferase
A pyridoxal 5'-phosphate enzyme. S-adenosylhomocysteine can also act as donor.
CAS REGISTRY NUMBER
COMMENTARY
37259-71-5
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + (S)-8-amino-7-oxononanoate
S-adenosyl-4-methylthio-2-oxobutanoate + 7,8-diaminononanoate
enzyme only uses (S)-8-amino-7-oxononanoate as substrate
-
-
?
S-adenosyl-L-methionine + 8-amino-7-oxononanoate
S-adenosyl-4-(methylsulfanyl)-2-oxobutanoate + 7,8-diaminononanoate
-
-
-
?
S-adenosyl-L-methionine + 8-amino-7-oxononanoate
S-adenosyl-4-methylthio-2-oxobutanoate + 7,8-diaminononanoate
pimeloyl-[acyl-carrier protein] + L-alanine
8-amino-7-oxononanoate + CO2 + holo-[acyl-carrier protein]
-
-
-
?
S-adenosyl-L-methionine + (S)-8-amino-7-oxononanoic acid
S-adenosyl-4-methylthio-2-oxobutanoate + (7S,8R)-diaminononanoate
-
-
-
?
S-adenosyl-L-methionine + 8-amino-7-oxononanoate
S-adenosyl-4-methylthio-2-oxobutanoate + (7S,8R)-diaminononanoate
S-adenosyl-L-methionine + 8-amino-7-oxononanoate
S-adenosyl-4-methylthio-2-oxobutanoate + 7,8-diaminononanoate
S-adenosyl-L-methionine + sinefungin
S-adenosyl-4-methylthio-2-oxobutanoate + ?
-
-
-
?
S-adenosyl-L-methionine + 8-amino-7-oxononanoate
S-adenosyl-4-methylthio-2-oxobutanoate + 7,8-diaminononanoate
-
-
-
?
S-adenosyl-L-methionine + 8-amino-7-oxononanoate
S-adenosyl-4-methylthio-2-oxobutanoate + 7,8-diaminononanoate
-
-
-
?
S-adenosyl-L-methionine + 8-amino-7-oxononanoate
S-adenosyl-4-methylthio-2-oxobutanoate + (7S,8R)-diaminononanoate
-
-
-
-
?
S-adenosyl-L-methionine + 8-amino-7-oxononanoate
S-adenosyl-4-methylthio-2-oxobutanoate + (7S,8R)-diaminononanoate
-
involved in the biosynthesis of biotin
-
-
?
S-adenosyl-L-methionine + 8-amino-7-oxononanoate
S-adenosyl-4-methylthio-2-oxobutanoate + 7,8-diaminononanoate
-
-
-
?
S-adenosyl-L-methionine + 8-amino-7-oxononanoate
S-adenosyl-4-methylthio-2-oxobutanoate + 7,8-diaminononanoate
ping pong bi bi kinetic mechanism with strong substrate inhibition
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + 8-amino-7-oxononanoate
S-adenosyl-4-(methylsulfanyl)-2-oxobutanoate + 7,8-diaminononanoate
-
-
-
?
pimeloyl-[acyl-carrier protein] + L-alanine
8-amino-7-oxononanoate + CO2 + holo-[acyl-carrier protein]
-
-
-
?
S-adenosyl-L-methionine + 8-amino-7-oxononanoate
S-adenosyl-4-methylthio-2-oxobutanoate + (7S,8R)-diaminononanoate
-
involved in the biosynthesis of biotin
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
PLP, invariant residue Lys283 is covalently linked to the PLP cofactor
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(R)-8-amino-7-oxononanoate
binds both to the pyridoxal 5'-phosphate form and to the pyridoxamine 5'-phosphate form by forming specific hydrogen bonds with residue T309 and the phosphate group of the cofactor
(Z)-N-(2-isopropoxyphenyl)-2-oxo-2-((3-(trifluoromethyl)cyclohexyl)amino)acetimidic acid
83% inhibition at 0.01 mg/ml
1-[4-[2-(2,5-dimethylbenzene-1-sulfonyl)ethyl]piperazin-1-yl]-4-methylpentan-1-one
-
2-(2-acetyl-5-methoxyphenoxy)-N-(1-phenylethyl)propanamide
-
2-([2-[(5-ethyl-4-propyl-1,3-thiazol-2-yl)amino]-2-oxoethyl]sulfanyl)-N-(5-methyl-1,2-oxazol-3-yl)propanamide
-
2-hydrazinyl-1,3-benzothiazole
reversible covalent inhibitor
2-oxo-6-phenyl-N-[2-[(prop-2-en-1-yl)carbamoyl]phenyl]-1,2-dihydropyridine-3-carboxamide
-
3-(cis-4-aminocyclohexa-2,5-dien-1-yl)propan-1-ol
suicide substrate, compound at 0.1 mg/l completely inhibits the growth of an Escherichia coli C268bioA mutant strain transformed with a plasmid expressing the Myobaterium tuberculosis bioA gene, coding for diaminopelargonic acid aminotransferase
3-[3-(2,3-dimethylcyclohexyl)-2-oxopropanamido]-N,2-dimethylbenzamide
-
4-(1H-imidazol-1-yl)benzamide
inhibitor identified by fragment library biophysical screening, induces Trp64 and Trp65 changes to widen the binding site, but also perturbs Tyr25. Binding induces a shift in melting temperature of +4.1 degrees
4-(bicyclo[2.2.1]heptan-2-yl)-N-(2-methoxy-5-nitrophenyl)-2-oxopentanamide
-
4-fluoro-N-(2H-indazol-6-yl)-3-(pyrrolidine-1-sulfonyl)benzamide
-
5-(pyridin-2-yl)thiophene-2-carboxamide
inhibitor identified by fragment library biophysical screening, induces a strong remodeling of the active site. Compound can inhibit the growth of virulent strains in biotin-deprived media. Binding induces a shift in melting temperature of +6.3 degrees
isopropyl 3-(2-(cyclopentanecarboxamido)propanamido)-3-(p-tolyl)propanoate
-
N-(1-isobutyl-1H-pyrazol-5-yl)-5-((2-methoxyphenoxy)methyl)furan-2-carboxamide
-
N-(2-[[2-(2,6-dichlorophenyl)ethyl]amino]-2-oxoethyl)-2-methylbenzamide
-
N-(tert-butylcarbamoyl)-N2-[2-(3,5-dimethylpiperidine-1-carbonyl)phenyl]glycinamide
-
N-ethyl-N-[(3-methylphenyl)methyl]-N'-[2-(morpholin-4-yl)-2-(oxolan-3-yl)ethyl]urea
-
N-methyl-1-[4-(1H-pyrazol-1-ylmethyl)phenyl]methanamine
inhibitor identified by fragment library biophysical screening, binding is purely enthalpie-driven. Binding induces a shift in melting temperature of +5.3 degrees
N-[(1-methyl-1H-imidazol-2-yl)(phenyl)methyl]-2-(propane-1-sulfonyl)acetamide
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N-[1-(butan-2-yl)-1H-pyrazol-5-yl]-5-(diethylsulfamoyl)-2-fluorobenzamide
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N-[4-[(2,6-dimethylmorpholin-4-yl)methyl]-1,3-thiazol-2-yl]-2-(2,4-dimethyl-6-oxo-1,6-dihydropyrimidin-5-yl)acetamide
-
N1-(2,3-dimethylcyclohexyl)-N2-(2-methyl-5-(methylcarbamoyl)phenyl)oxalamide
-
(Z)-N-(2-isopropoxyphenyl)-2-oxo-2-((3-(trifluoromethyl)cyclohexyl)amino)acetimidic acid
83% inhibition at 0.01 mg/ml
3-(cis-4-aminocyclohexa-2,5-dien-1-yl)propan-1-ol
suicide substrate, irreversible inhibition
isopropyl 3-(2-(cyclopentanecarboxamido)propanamido)-3-(4-tolyl)propanoate
about 25% inhibition at 0.01 mg/ml
N-(1-isobutyl-1H-pyrazol-5-yl)-5-((2-methoxyphenoxy)methyl)furan-2-carboxamide
about 10% inhibition at 0.01 mg/ml
N1-(2,3-dimethylcyclohexyl)-N2-(2-methyl-5-(methylcarbamoyl)phenyl)oxalamide
about 75% inhibition at 0.01 mg/ml
8-amino-7-oxooctanoic acid
achiral analog of 8-amino-7-oxononanoate
additional information
generation of a structure-based pharmacophore model using the three-dimensional crystal structure of DAPA synthase (BioA) (PDB ID: 3TFU), structure optimaztion and computational screening, virtual screening of compound libraries, docking study and enzyme-inhibitor-interaction analysis, overview
-
additional information
generation of a structure-based pharmacophore model using the three-dimensional crystal structure of DAPA synthase (BioA) (PDB ID: 3TFU), structure optimaztion and computational screening, virtual screening of compound libraries, docking study and enzyme-inhibitor-interaction analysis, overview
-
additional information
-
generation of a structure-based pharmacophore model using the three-dimensional crystal structure of DAPA synthase (BioA) (PDB ID: 3TFU), structure optimaztion and computational screening, virtual screening of compound libraries, docking study and enzyme-inhibitor-interaction analysis, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.7
sinefungin
pH 7.5, temperature not specified in the publication
0.45
S-adenosyl-L-methionine
pH 7.5, temperature not specified in the publication
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.012
S-adenosyl-L-methionine
pH 7.5, temperature not specified in the publication
0.009
sinefungin
pH 7.5, temperature not specified in the publication
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.03
S-adenosyl-L-methionine
pH 7.5, temperature not specified in the publication
0.013
sinefungin
pH 7.5, temperature not specified in the publication
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0017
(R)-8-amino-7-oxononanoate
binding to the the pyridoxamine 5'-phosphate form of enzyme, pH not specified in the publication, temperature not specified in the publication
0.0059
(R)-8-amino-7-oxononanoate
binding to the the pyridoxal 5'-phosphate form of enzyme, pH not specified in the publication, temperature not specified in the publication
0.014
3-(cis-4-aminocyclohexa-2,5-dien-1-yl)propan-1-ol
pH 8.6, 37°C
0.02
3-(cis-4-aminocyclohexa-2,5-dien-1-yl)propan-1-ol
pH 8.6, 37°C
0.0009
8-amino-7-oxooctanoic acid
binding to the the pyridoxamine 5'-phosphate form of enzyme, pH not specified in the publication, temperature not specified in the publication
0.0042
8-amino-7-oxooctanoic acid
binding to the the pyridoxal 5'-phosphate form of enzyme, pH not specified in the publication, temperature not specified in the publication
0.0017
(R)-8-amino-7-oxononanoic acid
bound to the pyridoxamine 5'-phosphate form, 100 mM EPPS buffer, pH 8.6
0.0059
(R)-8-amino-7-oxononanoic acid
bound to the pyridoxal 5'-phosphate enzyme form, 100 mM EPPS buffer, pH 8.6
0.0009
8-amino-7-oxooctanoate
bound to the pyridoxamine 5'-phosphate form, 100 mM EPPS buffer, pH 8.6
0.0042
8-amino-7-oxooctanoate
bound to the pyridoxal 5'-phosphate form, 100 mM EPPS buffer, pH 8.6
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
enzyme 7,8-diaminopelargonic acid aminotransferase (BioA) in Mycobacterium tuberculosis is primarily involved in the lipid biosynthesis pathway
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with inhibitors 5-(pyridin-2-yl)thiophene-2-carboxamide, 4-(1H-imidazol-1-yl)benzamide, and N-methyl-1-[4-(1H-pyrazol-1-ylmethyl)phenyl]methanamine
in complex with substrate 7-oxo-8-aminopelargonic acid and in complex with inhibitors 1-(1,3-benzothiazol-2-yl)methanamine and 2-hydrazinyl-1,3-benzothiazole. The side chains of Tyr25, Trp65, Arg400, and Tyr407 are shown to be quite flexible. Small molecule binding induces unexpected conformational remodeling in the substrate binding site
to 2.2 A resolution, by molecular replacement, and superimposition of the structures bound either to the S-adenosyl-L-methionine analog sinefungin or to 7-oxo-8-aminopelargonic acid. Comparison to structure of the Bacillus subtilis enzyme, EC 2.5.1.105
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
67
melting temperature, in complex with inhibitor 2-hydrazinyl-1,3-benzothiazole
78
melting temperature, in complex with inhibitor 1-(1,3-benzothiazol-2-yl)methanamine
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant soluble N-terminally His6-tagged enzyme from Escherichia coli by nickel affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression as mostly insoluble, N-terminally His6-tagged enzyme in Escherichia coli
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
analysis
simple, cheap, and sensitive microplate fluorescence assay for 7,8-diaminopelargonic acid aminotransferase activity, allowing linear detection of 7,8-diaminopelargonic acid in the range of 20 nM to 50 microM. The method relies on the direct detection in the enzymatic reaction mixture of the vicinal diamine 7,8-diaminopelargonic acid derivatized with ortho-phthalaldehyde and 2-mercaptoethanol. The assay was validated with the known inhibitor desmethyl-KAPA, i.e. 8-amino-7-oxopelargonic acid, and adapted to microplate for high-throughput screening
pharmacology
-
enzyme is a potential drug target in tuberculosis treatment
analysis
analytical method to measure the enantiomeric excess of substrate 8-amino-7-oxononanoic acid, based on the derivatization of its amine function, by orthophtalaldehyde and N-acetyl-L-cysteine, followed by high pressure liquid chromatography separation. Using this methodology and enantiopure samples of 8-amino-7-oxononanoic acid, it appears that racemization of 8-amino-7-oxononanoic acid occurs rapidly with half-lives from 1 to 8 h, not only in 4 M HCl but also in the usual pH range, from 7 to 9
analysis
simple, cheap, and sensitive microplate fluorescence assay, allowing linear detection of 7,8-diaminopelargonic acid in the range of 20 nM to 50 microM. The principle of the method is the direct detection in the enzymatic reaction mixture of the vicinal diamine 7,8-diaminopelargonic acid derivatized with ortho-phthalaldehyde and 2-mercaptoethanol. The assay is validated with inhibitor 8-amino-7-oxopelargonic acid and adapted to microplate
analysis
microplate fluorescence assay for 7,8-diaminopelargonic acid aminotransferase that is simple, cheap, and sensitive, allowing linear detection of 7,8-diaminopelargonic acid in the range of 20 nM to 50 microM. The principle of the method is the direct detection in the enzymatic reaction mixture of the vicinal diamine 7,8-diaminopelargonic acid derivatized with ortho-phthalaldehyde and 2-mercaptoethanol
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mann, S.; Marquet, A.; Ploux, O.
Inhibition of 7,8-diaminopelargonic acid aminotransferase by amiclenomycin and analogues
Biochem. Soc. Trans.
33
802-805
2005
Escherichia coli, Mycobacterium tuberculosis
Mann, S.; Ploux, O.
7,8-Diaminoperlargonic acid aminotransferase from Mycobacterium tuberculosis, a potential therapeutic target. Characterization and inhibition studies
FEBS J.
273
4778-4789
2006
Mycobacterium tuberculosis, Mycobacterium tuberculosis (P9WQ81), Mycobacterium tuberculosis ATCC 25618 (P9WQ81)
Mann, S.; Colliandre, L.; Labesse, G.; Ploux, O.
Inhibition of 7,8-diaminopelargonic acid aminotransferase from Mycobacterium tuberculosis by chiral and achiral anologs of its substrate: biological implications
Biochimie
91
826-834
2009
Mycobacterium tuberculosis, Mycobacterium tuberculosis (P9WQ81), Mycobacterium tuberculosis ATCC 25618 (P9WQ81)
Dey, S.; Lane, J.M.; Lee, R.E.; Rubin, E.J.; Sacchettini, J.C.
Structural characterization of the Mycobacterium tuberculosis biotin biosynthesis enzymes 7,8-diaminopelargonic acid synthase and dethiobiotin synthetase
Biochemistry
49
6746-6760
2010
Mycobacterium tuberculosis (P9WQ80), Mycobacterium tuberculosis, Mycobacterium tuberculosis CDC 1551 (P9WQ80)
Mann, S.; Eveleigh, L.; Lequin, O.; Ploux, O.
A microplate fluorescence assay for DAPA aminotransferase by detection of the vicinal diamine 7,8-diaminopelargonic acid
Anal. Biochem.
432
90-96
2013
Mycobacterium tuberculosis, Mycobacterium tuberculosis (P9WQ81), Mycobacterium tuberculosis ATCC 25618 (P9WQ81)
Shi, C.; Aldrich, C.C.
Design and synthesis of potential mechanism-based inhibitors of the aminotransferase BioA involved in biotin biosynthesis
J. Org. Chem.
77
6051-6058
2012
Mycobacterium tuberculosis (P9WQ81), Mycobacterium tuberculosis ATCC 25618 (P9WQ81)
Dai, R.; Wilson, D.J.; Geders, T.W.; Aldrich, C.C.; Finzel, B.C.
Inhibition of Mycobacterium tuberculosis transaminase BioA by aryl hydrazines and hydrazides
ChemBioChem
15
575-586
2014
Mycobacterium tuberculosis (P9WQ81), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WQ81)
Dai, R.; Geders, T.W.; Liu, F.; Park, S.W.; Schnappinger, D.; Aldrich, C.C.; Finzel, B.C.
Fragment-based exploration of binding site flexibility in Mycobacterium tuberculosis BioA
J. Med. Chem.
58
5208-5217
2015
Mycobacterium tuberculosis (P9WQ81), Mycobacterium tuberculosis H37Rv (P9WQ81)
Billones, J.B.; Carrillo, M.C.; Organo, V.G.; Sy, J.B.; Clavio, N.A.; Macalino, S.J.; Emnacen, I.A.; Lee, A.P.; Ko, P.K.; Concepcion, G.P.
In silico discovery and in vitro activity of inhibitors against Mycobacterium tuberculosis 7,8-diaminopelargonic acid synthase (Mtb BioA)
Drug Des. Devel. Ther.
11
563-574
2017
Mycobacterium tuberculosis (A5U255), Mycobacterium tuberculosis (P9WQ81), Mycobacterium tuberculosis, Mycobacterium tuberculosis ATCC 25177 (A5U255), Mycobacterium tuberculosis ATCC 25618 (P9WQ81), Mycobacterium tuberculosis H37Rv (P9WQ81)
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